Angiotensin-converting Enzyme Inhibitors and Early Sickle Cell Renal Disease in Children (MADREPIEC)
Patients with sickle cell anaemia may develop renal disease. In fact, renal disease occurred in 40% of adults patients (macroalbuminuria) with evolution to end-stage renal disease for half of them. Microalbuminuria is an early and sensitive marker of glomerular damage. It appears during the first decade and occurred in 20 to 25% of infants (2 to 18 years). Physiopathology of renal scarring is not well understood actually. Renal scarring might be due to glomerular hyperfiltration and vascular and endothelial damage. Angiotensin-converting enzyme inhibitors (ACE) were studied and used in diabetic nephropathy. In a study on 26 sickle cell adults, albuminuria was reduced about 50% by ACE compared to placebo after six months treatment. It might be interesting studying ACE efficacy in sickle cell children with microalbuminuria because renal disease is directly related to sickle cell and is not influenced by other cardiovascular risk factors like in adult patients.
We hypothesized to have a successful ACE treatment in more than 40% of cases after a nine months treatment period. A success is defined as a 50% reduction of the albuminuria/creatinuria ratio.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Interest of Angiotensin-converting Enzyme Inhibitors on Early Sickle Cell Renal Disease in Children. A Randomized, Double-blind Trial Enalapril vs Placebo.|
- Percentage of successful treatment of each arm [ Time Frame: at 9 months of treatment ] [ Designated as safety issue: No ]Successful treatment is defined by a reduction by half of the albuminuria/ creatinuria ratio (mg / mmol).
- Measure of albuminuria/ creatinuria ratio [ Time Frame: at 1, 3 and 6 month of treatment. ] [ Designated as safety issue: No ]
- Dosage of circulating forms of cell adhesion molecules ICAM-1 and VCAM-1 [ Time Frame: at the first day and at 9 months of treatment. ] [ Designated as safety issue: No ]
|Study Start Date:||June 2010|
|Study Completion Date:||June 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
|Placebo Comparator: 2||
Other Name: Glucose
Other Name: Enalapril
This is a multicenter study. In order to include 72 patients we should pre-include 400 patients.
They will be included in the study after signing the protocol consent. For final inclusion in the study, two albuminuria/creatinuria ratio should be over or equal to 3mg/mmol. If so, inclusion will be done and patient will be randomized (placebo/enalapril) by CLEANWEB software. A blood sample will be done.
Treatment tolerance will be check up at day 7 (blood sample for renal tolerance and clinical examination), month 1(clinical examination), month 3(clinical examination), month 6(clinical examination), and month 9 (clinical examination). Treatment efficacy will be evaluated by albuminuria/creatinuria ratio at month 1, month 3, month 6, and month 9. Physiopathology of ACE efficacy will be studied at first day and month 9 by dosage of ICAM-1 and VCAM-1.
Treatment plain posology (0.5mg/kg/day) will be progressively obtained on a three months period, beginning at 0.2mg/kg/day.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01096121
|Trousseau Hospital, Nephro-pediatric unit|
|Paris, France, 75012|
|Principal Investigator:||Tim ULINSKI, PH||Assistance Publique - Hôpitaux de Paris|